The gonococcal outer membrane is the cell component which interacts directly with the host, and thus, is of importance to the pathobiology and immunobiology of gonorrhea. The outer membrane structure of Neisseria gonorrhoeae is different from that of other gramnegative bacteria. These differences are responsible, in part, for the sensitivity of gonococci to some antibiotics and hydrophobic molecules. Gonococci vary with respect to their sensitivity to hydrophobic molecules: strains possessing the env phenotype are hypersensitive, whereas those with the mtr phenotype are relatively resistant. Preliminary data suggested that phospholipid head groups are exposed on the surface of env strains and that these groups are covered by a glycosylated outer membrane component in wild-type and mtr strains. The removal of the glycosylated outer membrane component in wild-type and mtr strains. The removal of the glycosylated determinants exposed phospholipd head groups and rendered the cell sensitive to inhibition by hydrophobic agents. We propose to determine the structure of the gonococcal outer membrane with respect to the extent of phospholipid bilayer regions by chemical analyses, phospholipase C-treatment, and use of non-penetrating reagents which can interact with surface phospholipids. In addition, the glycosylated outer membrane component responsible for masking phospholipid head groups will be characterized biochemically and related to the structure of the outer membrane. The heterogeneity of this component will also be determined. Further experiments will study the ecology of strains possessing relatively hydrophobe-impermeable outer membranes and the role of naturally occurring selective agents. The presence of increased glycosylated determinants on the cell surface can affect the surface charge and hydrophobicity of the cell. These properties will be examined by polymer partitioning and hydrophobic chromatographic techniques. Additional studies using phospholipase A-deficient mutants will assess the role of the endogenous phospholipase A as a potential virulence factor and in growth and autolysis of N. gonorrhoeae.